A Significant Influence of Metronidazole on Busulfan Pharmacokinetics: A Case Report of Therapeutic Drug Monitoring.

Research paper by Hyewon H Chung, Kyung-Sang KS Yu, Kyung Taek KT Hong, Jung Yoon JY Choi, Che Ry CR Hong, Hyoung Jin HJ Kang, Kyung Duk KD Park, Hee Young HY Shin, SeungHwan S Lee

Indexed on: 23 Mar '17Published on: 23 Mar '17Published in: Therapeutic drug monitoring


Busulfan is a cytotoxic agent used in preconditioning for hematopoietic stem cell transplantation (HSCT). Therapeutic drug monitoring of busulfan is necessary owing to its narrow therapeutic range. Patients undergoing preconditioning are susceptible to infection and might require co-administration of antibiotics. We present a case study of a three-year-old girl with precursor T-cell acute lymphoblastic leukemia who received intravenous busulfan before HSCT. Metronidazole was co-administered before the third dose of busulfan because of Clostridium difficile infection. The daily pharmacokinetic analysis revealed that the clearance reduced to 57% of that before the co-administration. Although the underlying mechanism is unclear, a significant pharmacokinetic interaction was observed between busulfan and metronidazole, underscoring the importance of therapeutic drug monitoring.